TY - JOUR
KW - autophagy
KW - chemo-resistance
KW - cholesterol biosynthesis
KW - cisplatin
KW - embryonic diapose
KW - minimal residual disease
KW - patient-derived tongue cancer organoids
AU - Miwako Sase
AU - Taku Sato
AU - Hajime Sato
AU - Fuyuki Miya
AU - Shicheng Zhang
AU - Hiroshi Haeno
AU - Mihoko Kajita
AU - Tadahide Noguchi
AU - Yoshiyuki Mori
AU - Toshiaki Ohteki
AB - The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both in vitro and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed “heritable” embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC.
BT - Developmental Cell
DA - 2024-11-05
DO - 10.1016/j.devcel.2024.10.007
N2 - The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both in vitro and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed “heritable” embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC.
PY - 2024
T2 - Developmental Cell
TI - Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease
UR - https://www.sciencedirect.com/science/article/pii/S1534580724006075
Y2 - 2025-01-13
SN - 1534-5807
ER -